英文药名：Signifor LAR(Pasireotide Injectable Suspension) 中文药名：帕瑞肽长效注射剂 生产厂家：诺华制药公司 药品介绍 近日，FDA批准诺华旗下的长效生长激素抑制剂类似物药物Signifor LAR（pasireotide，帕瑞肽）用于不适合手术治疗或尚未治愈以及第一代生长抑素类似物（SSA）控制不佳的肢端肥大症（acromegaly）成人患者的治疗。 Signifor LAR是新一代长效缓释剂型Signifor，每月肌肉注射（IM）一次，该药能够结合患者体内的生长激素抑制素受体，进而下调患者体内的生长激素和胰岛素类似生长因子-1（IGF-1）的表达水平，从根本上改善肢端肥大症患者病情，为第一代SSA控制不佳的肢端肥大症患者提供了首个可供选择的治疗方案。 在此前进行的2项多中心III期研究（C2402和C2305）中，Signifor LA达到其预期终点，即与第一代生长抑素类似物（奥曲肽LAR或兰瑞肽Autogel）治疗组相比，显著降低了患者的生长激素和IGF-1水平。 在今年11月，欧盟委员会也刚刚批准Signifor LAR用于肢端肥大症治疗。此前，Signifor已被欧洲和美国批准用于治疗肾上腺皮质机能亢进症（库欣病）。 Signifor LAR的获批，是基于2项多中心III期研究（C2402和C2305）的数据。2项研究结果均表明，与第一代生长抑素类似物（奥曲肽LAR或兰瑞肽Autogel）治疗组相比，Signifor LAR治疗组有更多的患者显著获得了生化控制（通过GH和IGF-1水平测定）。 据统计，目前全球肢端肥大症的发病率大约为百万分之六十。然而，由于诊断技术限制，在未来几年，其发病率可能会增加至这一数字的五倍还多。肢端肥大症不仅会导致患者的身体发育出现异常，由于体内激素水平的异常分泌，甚至会导致患者死亡的严重后果。因此，市场上也急需有效的治疗方案。诺华肿瘤部门负责人Bruno Strigini表示，此次FDA批准诺华公司的Signifor用于治疗肢端肥大症患者，为患者减轻病情痛苦提供了一种新的有效措施。 包装规格 Package Label – 20mg   NDC 0078-0641-81 Package Label – 40mg   NDC 0078-0642-81 Package Label – 60mg   NDC 0078-0643-81 Signifor LAR(Pasireotide for Injectable Suspension, for Intramuscular Use) Signifor LAR (pasireotide) Company: Novartis Approval Status: Approved December 2014 Treatment for: acromegaly Signifor LAR (pasireotide) is a somatostatin analog. Signifor LAR is specifically indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option. Signifor LAR is supplied as an injectable suspension for intramuscular injection. The recommended initial dose is 40 mg administered by intramuscular injection once every 4 weeks (every 28 days). For dose modifications please see drug label. Clinical Results SIGNIFOR® LAR (pasireotide) for injectable suspension, for intramuscular use INDICATION SIGNIFOR LAR is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option. IMPORTANT SAFETY INFORMATION Warnings and Precautions: Hyperglycemia and Diabetes: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. In the study of patients with acromegaly, five patients naïve to drug therapy exposed to SIGNIFOR LAR (two of whom were normoglycemic at baseline) were hospitalized for blood glucose in the range of 359-506 mg/dL and none in the active comparator group. Two additional patients who had received active comparator in the main trial and were switched to SIGNIFOR LAR in the extension trial were hospitalized for elevated glucose levels while on SIGNIFOR LAR treatment during the extension; one of those patients developed diabetic ketoacidosis. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. In the clinical development program, treatment with SIGNIFOR LAR caused an increase in the incidence of diabetes and pre-diabetes. A majority of patients, including those with normal glucose tolerance, pre-diabetes and diabetes, experienced increased glucose levels within the first 2 to 3 months of treatment with SIGNIFOR LAR. In the drug-naïve patient trial, the prevalence of diabetes increased from 30% at baseline to 60% at month 12. In the trial evaluating patients previously treated with somatostatin analogs, the prevalence of diabetes increased from 71% at baseline to 87% at month 6 in patients treated with SIGNIFOR LAR 40 mg and from 60% to 84% in patients treated with SIGNIFOR LAR 60 mg. Fasting plasma glucose and hemoglobin A1c should be assessed prior to starting treatment with SIGNIFOR LAR. In patients with poorly controlled diabetes mellitus, anti-diabetic treatment should be optimized before SIGNIFOR LAR treatment is started. Blood glucose monitoring should be done weekly for the first three months after initiating SIGNIFOR LAR and the first four to six weeks after dose increases. Periodic monitoring should continue thereafter, as clinically appropriate. Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic therapy(ies) or adjustment in the dose or type of anti-diabetic therapy(ies) per standard of care. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled despite medical management, the dose of SIGNIFOR LAR should be reduced or SIGNIFOR LAR should be discontinued. After treatment discontinuation, fasting plasma glucose and hemoglobin A1c should be assessed if indicated. Patients on anti-diabetic therapy discontinuing SIGNIFOR LAR may require more frequent blood glucose monitoring and anti-diabetic drug therapy dose adjustment to mitigate the risk of hypoglycemia. Bradycardia and QT Prolongation: Bradycardia Bradycardia has been reported with the use of SIGNIFOR LAR. Patients with cardiac disease and/or risk factor for bradycardia, such as history of clinically significant bradycardia, high-grade heart block, or concomitant use of drugs associated with bradycardia, should be monitored. Adjustments in the dose of drugs known to slow the heart rate (e.g., beta-blockers, calcium channel blockers) and correction of electrolyte disturbances, may be necessary when initiating or during the course of SIGNIFOR LAR treatment. QT Prolongation In cardiac electrophysiology studies (i.e. thorough QT studies) with SIGNIFOR s.c., QT prolongation occurred at therapeutic and supra-therapeutic doses. In the phase 3 trials, a corrected QT interval (i.e., QTcF) of greater than 480 ms was reported in four patients and an increase in the QTcF from baseline of greater than 60 ms was reported for 2 patients in the SIGNIFOR LAR arm. No patient on SIGNIFOR LAR had a QTcF value of greater than 500 ms. SIGNIFOR LAR should be used with caution in patients who are at significant risk of developing prolongation of the QT interval, such as those listed below: with congenital long QT prolongation. with uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina or clinically significant bradycardia. on anti-arrhythmic therapy or other substances that are known to lead to QT prolongation. with hypokalemia and/or hypomagnesemia. A baseline ECG is recommended prior to initiating therapy with SIGNIFOR LAR. Monitoring for an effect on the QT interval at the time of maximum drug concentration (21 days after injection) should be obtained in patients at risk. Hypokalemia or hypomagnesemia must be corrected prior to initiating SIGNIFOR LAR and should be monitored periodically during therapy. Liver Test Elevations: Increases in liver enzymes have been observed with SIGNIFOR LAR. Overall, in both phase 3 studies and across all doses, ALT or AST elevation greater than three times the upper limit of normal (ULN) were observed in 3% of patients and ALT or AST elevation greater than five times the upper limit of normal (ULN) were observed in 1% of patients treated with SIGNIFOR LAR. Assessment of liver function is recommended prior to treatment with SIGNIFOR LAR, and after the first 2 to 3 weeks, then monthly for 3 months. Thereafter, liver function should be monitored as clinically indicated. Patients who develop increased transaminase levels should be monitored until values return to pretreatment levels. Treatment with SIGNIFOR LAR should be discontinued if signs or symptoms suggestive of clinically significant liver impairment develop. Following discontinuation of treatment with SIGNIFOR LAR, patients should be monitored until resolution. Treatment should not be restarted, if the liver function abnormalities are suspected to be related to SIGNIFOR LAR. Cholelithiasis: Cholelithiasis was reported in 33% of drug-naïve and 10% of inadequately controlled (40 mg dose) acromegaly patients treated with SIGNIFOR LAR in clinical trials. Patients should be monitored periodically. Pituitary Hormone Deficiency(ies): Suppression of pituitary hormones other than GH/IGF-1, may occur on SIGNIFOR LAR. Monitoring pituitary function (e.g., thyroid, adrenal, gonadal) prior to initiation of therapy with SIGNIFOR LAR, as well as periodically during treatment, as clinically appropriate, is recommended. Patients should be monitored for and instructed on the signs and symptoms of adrenal insufficiency during therapy. If adrenal insufficiency is suspected it should be confirmed and treated per standard of care with exogenous glucocorticoids at replacement doses. Adverse Reactions Adverse drug reactions associated with SIGNIFOR LAR and occurring in ≥20% of patients were diarrhea (39%), cholelithiasis (26%), hyperglycemia (29%) and diabetes mellitus (31%). http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5504116c-d531-4d47-b160-41c6671d52aa